ZFP36-mediated mRNA decay regulates metabolism

Andrew C. Cicchetto; Elsie C. Jacobson; Hannah Sunshine; Blake R. Wilde; Abigail S. Krall; Kelsey E. Jarrett; Leslie Sedgeman; Martin Turner; Kathrin Plath; M. Luisa Iruela-Arispe; Thomas Q. de Aguiar Vallim; Heather R. Christofk

Cell Reports (May 2023)

ZFP36-mediated mRNA decay regulates metabolism

Andrew C. Cicchetto,
Elsie C. Jacobson,
Hannah Sunshine,
Blake R. Wilde,
Abigail S. Krall,
Kelsey E. Jarrett,
Leslie Sedgeman,
Martin Turner,
Kathrin Plath,
M. Luisa Iruela-Arispe,
Thomas Q. de Aguiar Vallim,
Heather R. Christofk

Affiliations

Andrew C. Cicchetto: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Elsie C. Jacobson: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Hannah Sunshine: Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Blake R. Wilde: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Abigail S. Krall: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Kelsey E. Jarrett: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USA
Leslie Sedgeman: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USA
Martin Turner: Immunology Programme, The Babraham Institute, Cambridge, UK
Kathrin Plath: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA
M. Luisa Iruela-Arispe: Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Thomas Q. de Aguiar Vallim: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Medicine, Division of Cardiology, UCLA, Los Angeles, CA, USA; Molecular Biology Institute, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA
Heather R. Christofk: Department of Biological Chemistry, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 5
p. 112411

Abstract

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Summary: Cellular metabolism is tightly regulated by growth factor signaling, which promotes metabolic rewiring to support growth and proliferation. While growth factor-induced transcriptional and post-translational modes of metabolic regulation have been well defined, whether post-transcriptional mechanisms impacting mRNA stability regulate this process is less clear. Here, we present the ZFP36/L1/L2 family of RNA-binding proteins and mRNA decay factors as key drivers of metabolic regulation downstream of acute growth factor signaling. We quantitatively catalog metabolic enzyme and nutrient transporter mRNAs directly bound by ZFP36 following growth factor stimulation—many of which encode rate-limiting steps in metabolic pathways. Further, we show that ZFP36 directly promotes the mRNA decay of Enolase 2 (Eno2), altering Eno2 protein expression and enzymatic activity, and provide evidence of a ZFP36/Eno2 axis during VEGF-stimulated developmental retinal angiogenesis. Thus, ZFP36-mediated mRNA decay serves as an important mode of metabolic regulation downstream of growth factor signaling within dynamic cell and tissue states.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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